Three different missense suppressor mutations isolated in strains of E. coli have been found to affect the GGG-specific glycine tRNA. These mutations alter the codon recognition of the tRNA to AGA, GAG and GAA, respectively. In addition to codon recognition, the biosynthesis and other functional aspects of the tRNA, such as amino-acylation, are affected by these mutations. The complete sequences of the wild type tRNA species and one of the mutant species have been solved, and current experiments are aimed at determining the change in primary sequence resultant from each of the other mutations, as well as at a complete functional characterization of these mutant tRNA's. This approach should provide insight into structure-function relationships on tRNA. We are also studying E. coli mutants which have tandem duplications of the glyT thi purD region. We have been able to isolate DNA derived from the tandem duplications. Using this DNA, we are studying the involvement of uneven recombination between ribosomal RNA genes in the generation of these chromosomal aberrations. Other factors influencing both the generation and segregation of tandem duplications are being investigated. These studies will contribute to our understanding of the nature and function of the genetic material, and thus will contribute to our understanding of diseases with a genetic basis. It should be emphasized that gross chromosomal aberrations are known to be prevalent in tumor viruses, malignant cells and, to a certain extent, in aborted fetuses; yet we know very little of the molecular events involved in illegitimate recombination.